SGLT2 Inhibitor Associated Ketoacidosis

Evaluate immediately for ketoacidosis in a patient taking an SGLT2 inhibitor who has nausea, vomiting, abdominal pain, generalized malaise, dyspnea, dehydration, or otherwise unexplained high-anion-gap metabolic acidosis. FDA labeling identifies under-insulinization, acute febrile illness, reduced caloric intake, ketogenic diet, surgery, volume depletion, and alcohol abuse as precipitants; symptoms may occur with glucose below the conventional DKA range. accessdata fda+2accessdata fda[PDF] FARXIGA® (dapagliflozin) tablets, for oral use - accessdata.fda.govaccessdata fda[PDF] QTERN® (dapagliflozin and saxagliptin) tablets, for oral usePubMedSGLT2 Inhibitor-associated Diabetic Ketoacidosis: Clinical Review and Recommendations for Prevention and Diagnosis. - Abstract

Euglycemic DKA is generally defined by ketosis and metabolic acidosis with glucose below 250 mg/dL. In the current global-consensus framework, DKA requires diabetes history or glucose at least 200 mg/dL, beta-hydroxybutyrate at least 3.0 mmol/L or urine ketones at least 2+ early in presentation, and metabolic acidosis. Thus, a patient with known diabetes, glucose 135 mg/dL, beta-hydroxybutyrate 4.5 mmol/L, and low bicarbonate meets the diagnostic framework despite no hyperglycemia. PubMed+2PubMedHyperglycemic Crises - Endotext - NCBI Bookshelf - NIHPubMedEuglycemic Diabetic Ketoacidosis - StatPearls - NCBI Bookshelf - NIHccjmClassic diabetic ketoacidosis and the euglycemic variant

Treat perioperative fasting, inability to eat, severe intercurrent illness, or missed basal insulin as a diagnostic escalation trigger rather than reassurance from a normal glucose value. Postoperative presentations may be mistaken for routine surgical recovery; early serum beta-hydroxybutyrate testing is specifically emphasized in cardiac surgical patients receiving SGLT2 inhibitors. Wolters Kluwer+1Wolters KluwerEuglycemic diabetic ketoacidosis with... : AME Case ReportPubMedEuglycemic Diabetic Ketoacidosis Associated With Sodium-Glucose Cotransporter-2 Inhibitors After Cardiac Surgery: A Review of Current Literature. - Abstract

Order serum or capillary beta-hydroxybutyrate, basic metabolic panel with calculated anion gap, venous blood gas, glucose, creatinine, and urinalysis in the initial evaluation. Beta-hydroxybutyrate at least 3.0 mmol/L supports DKA; an anion gap above 12 mEq/L is typical, but vomiting, renal bicarbonate loss, and mixed acid-base disorders can obscure the expected gap or pH. BMJ+1BMJDiabetic ketoacidosis - Diagnosis recommendations | BMJ Best Practice USPubMedHyperglycemic Crises - Endotext - NCBI Bookshelf - NIH

Direct beta-hydroxybutyrate is preferred to nitroprusside urine ketones for diagnosis and response assessment because urine testing does not directly measure beta-hydroxybutyrate and may be falsely positive with sulfhydryl drugs such as captopril or with valproic acid. A urine ketone result of 2+ or greater is an acceptable early diagnostic surrogate if beta-hydroxybutyrate is not immediately available. BMJ+1BMJDiabetic ketoacidosis - Diagnosis recommendations | BMJ Best Practice USPubMedHyperglycemic Crises - Endotext - NCBI Bookshelf - NIH

Venous pH is appropriate for serial monitoring and is usually approximately 0.03 units lower than arterial pH. A pH below 7.30 or bicarbonate below 18 mEq/L with ketonemia establishes clinically important ketoacidosis in euglycemic DKA descriptions; the global-consensus DKA approach requires metabolic acidosis in addition to ketosis. BMJ+2BMJDiabetic ketoacidosis - Diagnosis recommendations | BMJ Best Practice USPubMedHyperglycemic Crises - Endotext - NCBI Bookshelf - NIHPubMedEuglycemic Diabetic Ketoacidosis - StatPearls - NCBI Bookshelf - NIH

Discontinue the SGLT2 inhibitor immediately when ketoacidosis is diagnosed; FDA labeling instructs clinicians to assess for ketoacidosis regardless of glucose and discontinue dapagliflozin if suspected. Begin DKA-directed management with intravenous fluid resuscitation, insulin, electrolyte management, and carbohydrate replacement rather than withholding insulin because glucose is normal. accessdata fda+1accessdata fda[PDF] FARXIGA® (dapagliflozin) tablets, for oral use - accessdata.fda.govPubMedSodium-Glucose Transport 2 (SGLT2) Inhibitors - StatPearls - NCBI

Euglycemic presentations require special attention to carbohydrate replacement: insulin is needed to suppress ketogenesis, while dextrose-containing intravenous fluid may be needed to permit continued insulin administration without hypoglycemia. In a reported postoperative euDKA case, treatment with intravenous insulin added to 5% glucose-saline plus potassium, fluids, and nutritional support was associated with resolution of acidosis. Wolters Kluwer+1Wolters KluwerEuglycemic diabetic ketoacidosis with... : AME Case ReportPubMedSodium-Glucose Transport 2 (SGLT2) Inhibitors - StatPearls - NCBI

Identify and reverse the driver in parallel with metabolic treatment: restore reliable insulin delivery after omission or pump failure, address infection or acute illness, correct volume depletion, and re-establish caloric intake when feasible. Do not restart the SGLT2 inhibitor during the acute event; any later reconsideration requires reassessment of the precipitant, insulin reserve, and recurrence risk. accessdata fda+2accessdata fda[PDF] FARXIGA® (dapagliflozin) tablets, for oral use - accessdata.fda.govPubMedSGLT2 Inhibitor-associated Diabetic Ketoacidosis: Clinical Review and Recommendations for Prevention and Diagnosis. - AbstractPubMedSodium-Glucose Transport 2 (SGLT2) Inhibitors - StatPearls - NCBI

Before initiating an SGLT2 inhibitor, identify high-risk phenotypes: type 1 diabetes, insulin-deficient type 2 diabetes, prior or recurrent DKA, meal skipping, ketogenic or very-low-carbohydrate diets, excessive alcohol intake, and insulin pump use. SGLT2 inhibitors are not approved for glycemic control in type 1 diabetes, where estimated DKA incidence is approximately 4% and risk is reported as 5- to 17-fold higher than in untreated type 1 diabetes. accessdata fda+2accessdata fda[PDF] FARXIGA® (dapagliflozin) tablets, for oral use - accessdata.fda.govPubMedInternational Consensus on Risk Management of Diabetic Ketoacidosis in Patients With Type 1 Diabetes Treated With Sodium–Glucose Cotransporter (SGLT) Inhibitorsccjm9. Pharmacologic Approaches to Glycemic Treatment: Standards of Care in Diabetes—2025 | Diabetes Care | American Diabetes Association

For patients receiving SGLT2 inhibitors, temporarily withhold therapy during reduced caloric intake, dehydration, acute febrile illness, major illness, or other situations likely to cause ketosis. Reinforce that insulin should not be omitted or inappropriately reduced during sick days; if compatible symptoms develop, the next action is ketone and acid-base testing rather than home glucose-based reassurance. accessdata fda+2accessdata fda[PDF] FARXIGA® (dapagliflozin) tablets, for oral use - accessdata.fda.govPubMedSGLT2 Inhibitor-associated Diabetic Ketoacidosis: Clinical Review and Recommendations for Prevention and Diagnosis. - AbstractPubMedSodium-Glucose Transport 2 (SGLT2) Inhibitors - StatPearls - NCBI

For planned surgery, a 3- to 4-day preoperative interruption is recommended in perioperative reports to reduce euDKA risk. Clinical decisions in patients prescribed SGLT2 inhibitors for heart failure require individualized risk-benefit assessment because perioperative interruption may adversely affect cardiovascular risk, but ketoacidosis risk rises with fasting and surgical stress. Wolters Kluwer+2Wolters KluwerEuglycemic diabetic ketoacidosis with... : AME Case ReportWolters KluwerRisk of perioperative discontinuation of SGLT2... : BJA: British Journal of AnaesthesiaPubMedEuglycemic Diabetic Ketoacidosis Associated With Sodium-Glucose Cotransporter-2 Inhibitors After Cardiac Surgery: A Review of Current Literature. - Abstract